Our interest in the possible effects of vasoactive drugs on fibroblast and endothelial cell proliferation derives from 3 lines of research. The first is biochemical evidence that systolic ionized calcium increases quickly in response to a variety of polypeptide growth factors just as it does in response to vasoconstricting agents such as epinephrine vasopressin or angiotensin. Some polypeptide growth factors were reported to have vasoconstrictive activity while by the same token some of the classical vasoactive agents which are smaller peptides or aminoacid derivatives have been found to promote cell proliferation or hypertrophy. In addition, there are a number of conflicting reports suggesting that some vasodilating agents may over the long run lead to increased vascularity in the heart. Since such agents tend to lower intracellular calcium, an indirect action to cause endothelial cell growth (such as the effect of stretching, flattening, increased wall tension or increased turbulence or flow across these cells), might account for the cell growth. Thus, for a variety of reasons, it is of interest to see whether vasoconstricting or vasodilating drugs have any direct effect on the proliferation of cultured fibroblast and endothelial cells. We began with the study of 3T3 fibroblasts and, as reported in this abstract, found only modest growth enhancement of the vasoconstrictive substances in the physiological dose range. The vasodilating drugs neither promoted growth by themselves nor blocked the growth effect of serum. These results are being followed-up using these and other drugs on endothelial cells. If the results are similar, this would certainly indicate that the in vivo situation is much more complex and cannot be modelled by isolated cultures of pure cell populations.